Abstract We are requesting funds for the purchase of an Orbitrap Fusion Lumos tandem mass spectrometer and liquid chromatography system (Thermo Scientific) to be used for qualitative and quantitative proteomic analyses. This instrument will greatly expand the proteomic capabilities of the University of Rochester Mass Spectrometry Resource Laboratory and the services it offers to its user-base throughout the University of Rochester and Western New York. This instrument will fill critical gaps in our current proteomic capabilities including label free and isobaric quantitation, top-down analysis of intact proteins, analysis of post- translational modifications and deep coverage shotgun proteomics. Recent advances in mass spectrometry have provided powerful tools for high-throughput analysis of proteins that are widely employed in medical and biological research. Proteomic analyses are typically used for discovery applications and in clinical or analytical screens that require large-scale target detection and quantification of complex protein mixtures. Due to its potential for high impact on existing NIH-funded research programs and Centers, the University of Rochester Medical Center (URMC) has targeted proteomics as an area of critical development. The University's commitment to developing and supporting the Mass Spectrometry Resource Laboratory has been essential for providing accessibility to modern mass spectrometry resources, services and expertise for the University of Rochester and Western New York research communities. The facility has experienced a dramatic increase in demand in recent years, spurred in part by an overall shortage of accessibility to high-end mass spectrometers in the region. The requested Orbitrap Fusion Lumos mass spectrometer is a versatile instrument that excels at high- throughput and high-resolution applications, at a level far beyond the capabilities of the current mass spectrometers in the core facility. In this application, 11 major users and 2 minor users provide project descriptions that impact at least 13 NIH research grants. The diversity of users highlights the importance of this technology and the unmet level of need that will be addressed by the instrument. The need for sensitive high-throughput, high-resolution mass spectrometry is rapidly growing in the Medical Center and the College that encompass over 45 departments and research centers, and over 800 research laboratories. To ensure the highest level of access to proteomic technology and services, the requested instrument will be housed in the URMC Mass Spectrometry Resource Laboratory. Two dedicated core staff members will run the instrument, and the core staff and core director will manage projects, provide consulting, analyze data, and assist users with data interpretation and processing. Data storage, analysis, and processing will be performed at the University of Rochester's Center for Integrated Research Computing (CIRC), which manages a 144-core processor server for the facility. Institutional support and oversight will ensure that state-of-the-art mass spectrometry services are developed and accessible to the research community. !